Table 5. Site-Specific Major Bleeding Risk Among Patients Taking Non–Vitamin K Oral Anticoagulants for Nonvalvular Atrial Fibrillation With Concurrent Medicationsa.
| Concurrent Medication | Intracranial Hemorrhage | Gastrointestinal Bleeding | Bleeding in Other Sites | |||
|---|---|---|---|---|---|---|
| Adjusted Incidence Rate Difference (99% CI)b | Adjusted Incidence Rate Ratio (99% CI)b | Adjusted Incidence Rate Difference (99% CI)b | Adjusted Incidence Rate Ratio (99% CI)b | Adjusted Incidence Rate Difference (99% CI)b | Adjusted Incidence Rate Ratio (99% CI)b | |
| Atorvastatin | −5.37 (−7.25 to −3.49)c |
0.60 (0.49 to 0.73)c |
−8.83 (−11.89 to −5.77)c |
0.74 (0.66 to 0.83)c |
−0.28 (−1.02 to 0.45) |
0.85 (0.54 to 1.35) |
| Digoxin | 0.30 (−1.74 to 2.34) |
1.02 (0.85 to 1.23) |
−4.11 (−7.57 to −0.64)c |
0.89 (0.79 to 0.99)c |
−0.52 (−1.31 to 0.26) |
0.73 (0.43 to 1.21) |
| Verapamil | 0.42 (−4.23 to 5.08) |
1.03 (0.72 to 1.47) |
4.90 (−2.87 to 12.67) |
1.14 (0.92 to 1.40) |
1.00 (−0.79 to 2.79) |
1.53 (0.70 to 3.35) |
| Diltiazem | 1.24 (−0.92 to 3.41) |
1.09 (0.91 to 1.31) |
−4.18 (−7.81 to 0.01) |
0.90 (0.80 to 1.01) |
−0.49 (−1.31 to 0.33) |
0.77 (0.46 to 1.28) |
| Amiodarone | 8.14 (4.29 to 11.98)c |
1.97 (1.67 to 2.34)c |
5.64 (0.13 to 11.42)c |
1.20 (1.07 to 1.34)c |
0.21 (−1.17 to 1.60) |
1.15 (0.73 to 1.82) |
| Fluconazole | 44.16 (26.77 to 61.55)c |
3.03 (1.82 to 5.07)c |
93.65 (60.50 to 126.79)c |
2.18 (1.59 to 3.00)c |
1.91 (−3.61 to 7.43) |
1.86 (0.28 to 12.27) |
| Other azolesd | −14.42 (−35.18 to 6.33) |
0.30 (0.05 to 1.89) |
−23.84 (−58.69 to 11.02) |
0.59 (0.27 to 1.30) |
NA | NA |
| Cyclosporine | −8.02 (−33.90 to 17.87) |
0.57 (0.09 to 3.57) |
−19.51 (−64.69 to 25.66) |
0.66 (0.25 to 1.76) |
2.87 (−6.61 to 12.35) |
2.15 (0.16 to 29.06) |
| Erythromycin or clarithromycin | −12.65 (−19.41 to −5.89)c |
0.48 (0.30 to 0.76)c |
−29.65 (−41.41 to −17.88)c |
0.59 (0.46 to 0.77)c |
1.41 (−1.04 to 3.86) |
1.46 (0.57 to 3.77) |
| Dronedarone | −2.60 (−6.70 to 1.50) |
0.73 (0.43 to 1.24) |
−2.91 (−10.01 to 4.20) |
0.89 (0.68 to 1.18) |
1.03 (−0.68 to 2.74) |
1.65 (0.71 to 3.86) |
| Rifampin | 17.02 (0.51 to 33.53)c |
0.48 (0.30 to 0.76)c |
15.56 (−15.24 to 46.35) |
1.32 (0.77 to 2.27) |
4.04 (−1.60 to 9.67) |
3.43 (0.54 to 21.65) |
| Phenytoin | 50.38 (42.94 to 57.81)c |
4.62 (3.52 to 6.05)c |
0.92 (−11.42 to 13.26) |
1.02 (0.75 to 1.38) |
1.90 (−0.87 to 4.67) |
1.94 (0.70 to 5.37) |
Abbreviation: NA, not applicable.
For more details, see eTable 5 in the Supplement.
Incidence rate difference indicates the difference in incidence rates between person-quarters exposed to a non–vitamin K oral anticoagulant with or without concurrent medication. Adjusted by inverse probability of treatment weighting using the propensity score (sex, age, medical utilization, chronic kidney disease stage, anemia, myocardial infarction, congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, rheumatic disease, peptic ulcer disease, mild liver disease, diabetes, hemiplegia or paraplegia, any malignancy, moderate or severe liver disease, metastatic solid tumor, acquired immune deficiency syndrome, percutaneous coronary intervention, coronary artery bypass surgery, transient ischemic attack, hypertension, aspirin, clopidogrel, ticagrelor, ticlopidine, warfarin, glucocorticoids, insulin, lipid-lowering agents, hypoglycemic agents, antihypertensive, nonsteroid anti-inflammatory drugs, proton pump inhibitors, residence, income level, and occupation).
P value was less than .01.
Other azoles include ketoconazole, itraconazole, voriconazole, or posaconazole.